As a charity that is focused solely on raising funds to support research into treatment for Rett Syndrome and related MECP2 disorders, we talk a lot about finding a cure. But how will this happen? What do we mean by a ‘cure’? Why do we think there are such strong grounds for hope that an effective treatment is within sight?

To understand this, it’s important to understand what causes the condition. Rett Syndrome is caused by a single gene called MECP2 that mutates – changes permanently – at the point a child is conceived. It is this mutation that means the child will go on to have Rett Syndrome.

The MECP2 gene can mutate in a variety of different ways. Genetic testing – which is often used to confirm a Rett diagnosis – can pinpoint the exact type of mutation a child has. And parents often ask at this point what the prognosis is. As parents, we’ve all asked it: “What does this particular mutation mean for my daughter? How severely affected is she? What will she be able to do?”

But it isn’t quite that straightforward. There is no simple correlation between mutation-type and severity of Rett-symptoms.

Instead, there are two main explanations for differences in severity between different individuals – and understanding these will help us move towards effective treatments.

The first explanation is different patterns of X chromosome inactivation.

This refers to the number of cells in a girl’s body in which the mutated gene is active. The mutated MECP2 gene is on the X chromosome. Females have two X chromosomes – and in every cell of their body, one X chromosome is ‘active’, and the other is ‘silent’.

This active/silent pattern is usually random, which means that around 50 per cent of cells have one active X chromosome and 50 per cent have the other. But sometimes this pattern is not random, but appears skewed – where one chromosome is ‘favoured’ over the other.

If a girl with Rett Syndrome has a skewed pattern where the X chromosome with the mutated MECP2 gene is active in more cells than not, her symptoms will be more severe. (And vice versa – if the X chromosome with the healthy MECP2 gene is more active, she will be less severely affected.) We know from looking at identical twins with Rett Syndrome, who have the exact same mutation but different symptoms, that different patterns of X chromosome inactivation can make a significant difference.

If researchers could find a way of switching on the X chromosome with the healthy MECP2 gene – in every cell of the body – Rett Syndrome could potentially be cured.

The second explanation for differences in severity is the existence of modifier genes.

Looking at all kinds of diseases, we can see that the same disease affects different individuals in different ways. One reason for this is ‘modifier genes’ – something in a person’s unique genetic makeup that protects them against some aspects of the disease. Evidence suggests that some girls with Rett Syndrome have other genes that counteract the effects of MECP2 mutation.

If researchers could identify which genes protect against Rett Syndrome, treatment could be developed based on introducing these modifier genes.

The funds Reverse Rett raises in the UK are allocated to a range of research projects that aim to find treatment based on what we know about what causes Rett Syndrome and what affects the severity of the condition for individual girls.

There are three main approaches.

1. MECP2 as the target

We are particularly keen on this approach, because it attacks Rett Syndrome at its very root by seeking to switch off the mutated gene and switch on the healthy one. Research taking place at the University of North Carolina at Chapel Hill by Dr Ben Philpot and colleagues aims to activate the silent X chromosome that contains the healthy MECP2 gene. A big advantage of this approach is that there would be no need to deliver the healthy gene through gene therapy – because every girl with Rett Syndrome already has a healthy copy of the MECP2 gene.

2. Suppressor (modifier) genes

This is an example of the type of high-impact, high-risk project that we are keen to fund – because the potential rewards are so great. The aim is to identify which genes have the effect of suppressing, or modifying, the effects of the mutated MECP2 gene, as described above. It’s a bit like searching for the proverbial needle in a haystack. But Dr Monica Justice and colleagues at Baylor College of Medicine are beginning to see results. They are 15 per cent of the way through a project to ‘screen’ genes, and have so far found five potential ‘modifier’ genes.

One of the benefits of this approach is that it is helping researchers gain a better understanding of MeCP2, the protein produced by a normal, unmutated MECP2 gene. The exact function of this protein isn’t yet well understood, but one of the things it does is regulate other genes involved in brain function. It helps nerve cells (neurons) to function and to connect with each other. Girls with Rett Syndrome lack this protein, and as a result the neurons in their brain don’t connect as they should. (They don’t have brain damage: it’s the synapses – the points of communication between brain cells – that aren’t working normally.)

3. Downstream targets

We don’t always need to start from scratch with every treatment. There are drugs and treatments that are currently used to treat other conditions, but that may also have the potential to improve some of the most challenging symptoms of Rett Syndrome, such as breathing problems, seizures and disordered movements. Trials are already taking place in a number of locations, and we await the results.

This month we transferred £200,000 (just over $300,000) to the research projects we support in the US – one of the highest quarterly amounts we’ve ever sent. It’s such a good feeling to sign the transfer and send it off, knowing that it’s going to support the researchers who are as committed as we are to solving the puzzle that is Rett syndrome.

Every time we transfer money we are conscious that we are transferring along with it the hopes and dreams of families who love someone with Rett syndrome or a related MECP2 disorder. Our network of dedicated fundraisers – people who are determined to change the future for our children – is rooted in personal connections and in knowing what treatment would mean for those families.

The most powerful thing we can do as individual parents is to tell our stories. Everyone who donates money to the charity, or sponsors someone to do something, or holds an event, or whatever it may be, has been motivated to do it by hearing a story. Hearing about one child and their family: their parents, their siblings, the world they live in. Hearing about love and loss, about adjusting to things that are unimaginably difficult, about holding on to faith in your child and hope for their future.

It’s hard to do, no question about it. It takes a lot to stand up in front of people, or talk to the local newspaper, or just spell out for friends, colleagues and neighbours what’s going on in our lives. It can make us feel uncomfortably exposed.

And yet at the same time it creates connections that go deeper than almost anything else in our day to day lives. It makes people want to help. They want to know what they can do, and to feel part of something as momentous as driving forward the science that will, one day, make a diagnosis of Rett syndrome easier to bear.

Setting out the rational arguments for why there is hope for children with Rett syndrome and related MECP2 disorders is at the heart of what we do. We don’t believe in magic, and we’re not hoping for the best. Working with scientists, explaining the research, building on what we know about MECP2 (the gene that mutates to cause Rett syndrome) to find a way of making our children’s lives easier – it’s all central to our task. But telling a story is what makes appealing for funds to support the research so compelling. And the power to do it is in your hands.

Everyone who lives with Rett syndrome knows there’s a chance that, one day, you won’t be living with it any more. You hear – too often – about the death of someone’s child, and you try to imagine how it would feel if it were your family facing such a loss.

We all know about it, but we try not to dwell. We put our energies into looking after our daughters, making sure they have everything they need, and trying to make their lives as good as possible. With any leftover energy, we try to learn about Rett syndrome and the potential for treatment, and we raise funds for research.

But sometimes something happens that makes you focus particularly hard on what your family lives with – and what the future might hold. This weekend news outlets in the UK have been filled with reports about the very sad death of Rosie McLoughlin, the 14-year-old sister of Coleen Rooney, wife of the English footballer Wayne Rooney. It’s clear from the news reports that her family loved her very much. And it’s sad that it takes a tragic loss like this to bring Rett syndrome into the news, given both its prevalence (it’s as common as cystic fibrosis) and its potential for treatment.

Hearing Rett syndrome being talked about in the context of one family’s loss reminds parents of why we do what we do: not just looking after our children and advocating for them, but raising funds for the research that we believe will transform our daughters’ futures. It renews our determination not to accept that nothing can be done, and reminds us of the hope engendered by recent progress in Rett research.

We do what we do because we don’t want any more families to watch their children deteriorate. Because we don’t want girls with Rett syndrome to be trapped in their bodies for a second longer than they have to. And because we want to speed the research to its logical conclusion: a treatment and cure for Rett syndrome.

A paper published online today in the high-profile journal, Nature, describes the results of using bone marrow transplant to dramatically stop the development of symptoms in pre-symptomatic male and female mouse models of Rett Syndrome. The work was undertaken in the neuroimmunology laboratory of Jonathan Kipnis, Ph.D. and his team at the University of Virginia. That a bone marrow transplant could arrest such a severe neurological syndrome such as Rett is quite unexpected and provides us with yet another strong example of how tractable this disorder appears to be – at least in the animal models. Experiments are now underway in the Kipnis lab to test whether reversal of advanced symptoms via bone marrow transplants and other modulation of the immune system is also possible.

The clinical relevancy of this work makes this paper of obvious and significant interest. But the authors don’t stop there. The paper describes data that could help us better understand how MeCP2 deficiency leads to symptoms.

They introduce the concept of a powerful connection between the immune system and Rett Syndrome and open the door not only to bone marrow transplants as a treatment modality but potentially to other immune therapies as well.

Please visit our website to read the press release and to view an animation of the experiments and a video interview with Monica Coenraads of RSRT, Dr. Kipnis and his lab members, Noël Derecki and Jim Cronk.

Translations of the press release are available in Spanish, Italian, Portuguese, German, Chinese, Russian.

Rachael Bloom, Executive Director of Rett Syndrome Research Trust UK says, ‘On behalf of all of us at Rett Syndrome Research Trust UK, it is an honour to have even been shortlisted from so many amazing entries for this award. To win was something else. But this recognition is more than an accolade for an organisation; it is testament to the determination and hard work of our fundraisers up and down the country who have done anything and everything they can to raise the vital research funds we need to reverse Rett in our children’s lifetimes.’

Donors, supporters and fundraisers; thank you for everything you do and huge thanks to Just Giving for making it so much easier.

Great congratulations and appreciation also goes to Kelly Phillips, Finalist in thePayPal Fundraiser of the Year category, for her tireless fundraising for Rett Syndrome Research Trust UK

We would also like to thank the team at Beyond Analysis for coming to support us on the night and for all their efforts to help us impact the speed at which treatment can be delivered for our children with Rett Syndrome.And last but definitely not least, thank you to our girls and women with Rett for hanging in there with us, giving us so much inspiration through what they endure every single day.

Fundraising through Just Giving is free and easy. You can set up fundraising pages in celebration, for challenges and events, in memory or actually for any reason at all. 2012 is set to be a pivotal year for Rett research. You can be part of it.

Since the inception of the charity in July 2010, Kelly has been an avid supporter and super successful fundraiser for Rett Syndrome Research Trust UK. We welcome Kelly’s single-mindedness, her determination and her ‘everything’s possible’ attitude.

Kelly’s interest in Rett research began the moment that her daughter, Harriet was diagnosed with Rett Syndrome in December 2007. Like most parents receiving the devastating news that their child has a debilitating condition for which there is currently no treatment, Kelly’s immediate response was to find out what she could do to ameliorate the situation for Harriet.

Since launching Hope for Harriet in Sept 2010, Kelly and her supporters have already raised in excess of £50,000 for Rett Syndrome Research Trust UK. As a Trustee, Kelly will work to develop and implement a fundraising strategy that will enable more families to raise significant funds to help drive the science forward, with a particular emphasis on community fundraising projects like Hope for Harriet.

‘I believe a cure is possible but I’m nervous about the timeframe. I’m scared something is going to happen to Harriet. I want to see a cure in her lifetime, but we don’t know how long her lifetime is. So while there is a chance to deliver treatment, I’m going to be involved in it. I’m not going to waste a day crying. I’m going to do what I can.’

It’s only February and already so many amazing things have come out of working with Beyond Analysis. From their January burn-the-fat aerobics to prolific Valentine’s bake sale, from awesome Rett infographic to awareness raising article in none other than Third Sector Magazine, Beyond Analysis have already made some serious headway in terms of their impact on the effort to reverse rett. Infact, they have created such a vibe with all their efforts that it’s got people talking-which is great, except when we get to that question that inevitably sends us on the errrr….ummm road.

You see, until this week, we haven’t properly understood what it is that Beyond Analysis actually do.Even after visiting their offices a couple of times (think cool, big windows, swift working, fast moving, super clever people with a few lovely dogs meandering around) it somehow remained a total mystery. Yes, we could give you the blurb: BA are a leading customer insight and strategy business..etc. etc. but we still didn’t really get it until Wednesday of this week when we had the second of our monthly workshops with the Beyond Analysis team. This time the meeting was focused on data; an utterly terrifying word for those of us who are adverse to numbers or maths of any sort (me).

And here’s the magic. We thought we had just sent the team at BA a bunch of numbers. And, if we can be honest, not a very good bunch of numbers, because (if we are being honest) collecting numbers and information is not something we’ve done a great job at yet. But here’s what they did. They took the sparse information we gave them, cleaned it up, broke it down, turned it inside out and upside down and used it to ask questions that we’d never even thought of.

They made us think outside the box about who supports us and why and who else might support us, the different ways and reasons we might draw them in, and how, when these different people arrive at planet reverse rett with all their different reasons for touching down wherever they do (calling us, writing to us, googling us, facebook, twitter, blog,Just Giving) how we can give them theirbest opportunity to do something to impact the effort to speed treatment for Rett Syndrome.

And that’s what Beyond Analysis do. They take information; facts, statistics, (yess, data…) and they make it human. They don’t just look at a fact the way we might, as it stands, on the face of it and see it as a static thing. They unearth the driving forces behind it and from that perspective are able to elucidate the best possible pathways in terms of next steps that will benefit, (in our case) the supporter, the organisation and as always, above all, those research projects which are so critical for our children’s future.

Thank you, to everyone at Beyond Analysis for their continued support and general genius

Excavated Fact: Did you know that while only 6% of people who make direct donations to Rett Syndrome Research Trust UK add a message, those people represent 40% of the spend?

And just when you might be thinking it’s all brain not brawn-check this out.This weekend, three of the brilliant BA-ers are running the horrifically named ‘Slay the Dragon’ 10K to raise funds for Rett Syndrome Research Trust UK. Big thanks and best wishes to Will, Sam and Paul. We wish you good luck and THANK YOU for doing what you can to help speed treatment for our children with Rett Syndrome. http://www.justgiving.com/BAslaythedragon

The following extracts are from a Facebook conversation between Nicky Perriman, mum to Robyn and Rachael Bloom, Executive Director of Rett Syndrome Research Trust UK and mum to Amber in response to the following Facebook post:

Rachael Bloom ‘2012 may see the efforts of the scientists and the donors who support them begin to bear fruit – a year that could prove to be paradigm-shifting in how we think about fighting Rett Syndrome. A year where we may begin to test, via clinical trials, whether what works in the animal models will actually work in children.’

Nicky Perriman I wait in hope as does every other Rett Syndrome mother/father…. But I feel we are being led up the garden path. I have recently looked into Rett research for the first time in my life since my child’s diagnosis…. Several times I have come across how this has been reversed in mouse models, each stating that you are still unsure that you can reverse it in humans… I remember going to the Rett Syndrome Association Family Weekend when Robyn was first diagnosed and being told about reversals in mouse models (or it was close) I remember being young and naive, and very new to Rett and looking at these mice and being sucked in that a difference could be made. Years later our cure is still no closer-the research doesn’t seem to have come much further. Now this is either my failure to read properly or my hopes are too high.

Rachael Bloom@Nicky Perriman, I am really glad you have asked these questions because this is certainly something that a lot of people are talking about and questioning and it’s important that we get it out in the open and discuss.

As you know, Rett Syndrome is most commonly caused by a gene called MECP2 which makes a protein, also called Mecp2, which is necessary for normal brain function. When the reversal was done in the mice, the researchers did it by genetically engineering the mice so that they had a ‘switch’ whereby, they could let the mice develop without the protein (they developed Rett symptoms) and then switch the protein back on at will (the symptoms went away). Our children don’t have a switch, so it was not possible, after the reversal experiments, to just translate what happened in the mice, into humans. Researchers have to find other ways to restore the protein at the right levels.

So in collaboration with US based RSRT; Rett Syndrome Research Trust UK has funded 12 treatment-focused projects in the last 18 months. Some of these are looking at how to replace the protein at the right levels; some are looking at addressing the underlying problems with the gene. Some are looking at bypassing the faulty gene, or finding ways to use other genes to help counteract the problems with MECP2. Others are looking at improving specific symptoms, or even just improving the symptoms at large without having to address the underlying genetic causes.

Nicky Perriman Well that sounds pretty good… A month ago that woulda gone right over my head lol. Would you think I’m correct in thinking that, this cure, protein replacement etc. would benefit younger girls i.e. recently diagnosed. Not that I’m being pessimistic but I just think if Robyn received a cure/reversal of any kind she would still be behind X amount of years. She would have to start learning from being a newborn baby. Sorry to pose these questions x

Rachael Bloom They are good questions. The data from the reversal experiments shows that the reversal was effective in models of late stage disease. The quote from the abstract from the paper cited above says: Using a mouse model, we demonstrate robust phenotypic reversal, as activation of MeCP2 expression leads to striking loss of advanced neurological symptoms in both immature and mature adult animals.

Nicky Perriman I also want to know if they know what will the reversal mean to us? i.e. if they do find a way to put the protein back? Is it expected to cure the epilepsy etc.? x

Rachael Bloom Let’s start by clearing up the difference between treatments for Rett and a cure for Rett. An effective treatment should really help or even take away a particular symptom or set of symptoms. As you know firsthand, there are so many severe symptoms that make up ‘Rett Syndrome’ that even controlling one or two could dramatically improve a person’s quality of life. A cure on the other hand, should completely restore someone to health. Until whatever treatments and cures become available for and are tested through human trials, no one can say exactly what is going to happen. Certainly, the videos of reversal in the mouse model show a dramatic regain in function. See here for before:

and here for after:

the mice do go on to live normal lifespans, where, without reversal, they died within days.

Nicky Perriman Yes I saw that. It’s very exciting stuff, I just wonder how it’s all going to work x

Rachael Bloom I think we all do. And the answer is that we just don’t know. My daughter is sixteen now. I can’t predict how she will respond to treatments and cures when they come. What I hope, is that, after a lifetime of disabilities and medical complexities, they give her a chance to live more freely and maybe even the chance to improve on some things, to be able to benefit from therapies, to make actual progress, instead of working so hard all the time just to bat a barrage of difficult symptoms off. I want to make one thing clear though; there are some people who get involved with causes and charities because they are nice people who care about the whole world. That isn’t me. I can hear my daughter struggling to breathe every night when I go to bed. The fact that the scientific evidence is there to support the fact that reversal is hypothetically possible for models of late stage disease is what gets me out of bed in the morning.

Nicky Perriman I feel so sorry for the mice, and I hate mice. But I know it’s essential for our girls to have treatment.

‎Rachael Bloom🙂 re mice. I’m a vegetarian-never eaten a mouse in my life but I feel more sorry for our girls.

Nicky Perriman Oh yes indeed. I’m petrified of mice lol. On a positive note I actually see Robyn purposely dancing just her head, but it was to the beat. It was amazing. Her dystonia is so bad and 3 of us notice these tiny head movements. It’s lovely when you see a simple thing like that they we take for granted. All I want is for her Dystonia to be controlled, that’s all I ask loll x

Rachael Bloom I would take breathing x

Rachael Bloom Just going back to Monica’s letter though…despite the fact that we have now had almost five years of knowing about reversal and rumblings of treatments and cures where there were none before, the thing that was different about Monica’s letter, was that this is the first time RSRT (US) has publically stated that we are moving into a time where research coming out of the lab may have real clinical implications: ‘2012 may see the efforts of the scientists and the donors who support them begin to bear fruit – a year that could prove to be paradigm-shifting in how we think about fighting Rett Syndrome. A year where we may begin to test, via clinical trials, whether what works in the animal models will actually work in children.’

There’s a reason that this needs to be said, and it isn’t about raising hopes -it’s because it will cost a lot of money to take this work to the next stage and we need help. These are good problems to have though-hope/yes/no-bad or good? (Great to have a choice, there wasn’t one when Amber was diagnosed) Need more money to ensure promising research developments can be carried through to the next level?? Scary…and a lot of work…but better than more years of no next level to move to… Will we get an all-out cure (get up and walk Lazarus!) or just significant improvements??….either of these and anything in between are surely better options than what is currently available, I think. I hope. Yes, I do. I do hope! Every day. I think it’s allowed. And I am waaayyy way down that garden path. And funnily enough, there are a lot of scientists here too:)

The evening of December 1st was a very special evening for us. So often as parents of daughters with Rett Syndrome, we face what we face alone. Looking around 3 Olaf Street that night, the room milling with people all there to show their support for our endeavour to speed treatment for our children, was nothing short of breath-taking and one which will carry many of us through dark moments which may be to come.

But that’s not all you will carry. On that night, through your generosity and commitment we raised an amazing £273,000 which will be immediately invested in the high-impact science projects we support.

The future of children and adults suffering with Rett Syndrome has never looked brighter. We fervently believe that reversing the symptoms of Rett Syndrome is possible. When that day comes you will know that you played a key role in our success.

Thank you is inadequate but we say it anyway. Thank you to our gracious hosts and event committee. Thank you to our kind sponsors. Thank you to all of you who donated auction or silent auction items and to all of you who bid and won them. Thank you to all the companies and individuals who gave their time, energy and resources, often pro bono to make this event a success. And last but definitely not least, thank you to all of you for coming, for buying tickets and tables and programme space, for making pledges and donations; for listening to our story and for becoming part of it.

I’d rather be climbing a mountain than doing this. But after doing that row last week it is nice to be standing up.

There’s not many things that are good about this diagnosis but it does really put things into perspective. Beth’s mum and I split up before she showed any signs of Rett syndrome. She moved a little way from me, closer to Liverpool. All I could think about was how awful it would be if she ended up with a scouse accent.

The worst thing about Rett syndrome is that every year something new happens that is worse than the year before.

Beth is eleven now and her back is so bent that she can’t sit up properly anymore. She’s struggling to hold her head up; she’s stopped being able to walk. Sometimes she can’t even stand.

In January, Beth is having a metal rod attached to her spine. I’m terrified about the length of the surgery; the amount of anaesthetic that’ll be needed. The surgeon called it a controlled car crash. Who wants to put their daughter forward for one of those?

Beth was a really bright baby, looking at everything, bringing me toys, looking for my approval and then it all stopped. She stopped moving-she just sat there rocking, wailing, crying, distressed; nothing could calm her down.She did speak. Just a few words. She never even got as far as saying dad.

I don’t need a cure for Beth, not for myself. I’ve never needed her to have a wedding, or have children, or do anything for me. I’ve never felt like I lost anything, I’ve always felt like I’ve gained something by having her. But I want it for her. I want her to be able to say whether she likes what I’m giving her to eat or if she wants something else. I wonder what it would be like for her to have friends.

Beth is waiting. That’s what I say when people tell me they haven’t got around to getting their sponsor money in. That there’s a girl here, stuck in her wheelchair, can’t move, bent over double. Waiting for treatment that will be delivered if we can all just keep the funds coming in.